tbuckley/cabot-search huggingface dataset:
Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro
Authors: Peilin Zhang, Wei Gao, Steven Turner, Barbara S Ducatman
Journal: Molecular Cancer (2003)

Gleevec (aka STI571, Imatinib) is a recently FDA approved anti-tumor drug for chronic myelogenous leukemia. Gleevec binds specifically to BCR-ABL tyrosine kinase and inhibit the tyrosine kinase activity. It cross-reacts with another two important membrane tyrosine kinase receptors, c-kit and PDGF receptors. We sought to investigate if Gleevec has a potential role in treatment of non-small cell lung cancer. We have shown that Gleevec alone can inhibit the A549 lung cancer cell growth in dose-dependent manner, and the optimal concentration of Gleevec inhibition of A549 cell growth is at the range of 2–3 μM (IC50). We have also shown that A549 cells are resistant to cisplatin treatment (IC50 64 μM). Addition of Gleevec to the A549 cells treated with cisplatin resulted in a synergistic cell killing effect, suggesting that Gleevec can potentiate the effect of cisplatin on A549 cells. We also showed that the A549 lung cancer cells expresses the platelet derived growth factor receptor α, and the inhibitory effects of Gleevec on A549 cells is likely mediated through inhibition of PDGFR α phosphorylation. We further tested 33 lung cancer patients' tumor specimens to see the frequency of PDGFR-α expression by tissue micro-arrays and immunohistochemistry. We found that 16 of the 18 squamous carcinomas (89%), 11 of the 11 adenocarcinomas (100%), and 4 of the 4 small cell lung cancers (100%) expressed PDGFR-α. These results suggest a potential role of Gleevec as adjuvant therapeutic agent for treatment of non-small cell lung cancer.
Endogenous/Exogenous Nanovaccines Synergistically Enhance Dendritic Cell‐Mediated Tumor Immunotherapy
Authors: Yu Zhang, Qiang Li, Meng Ding, Weijun Xiu, Jingyang Shan, Lihui Yuwen, Dongliang Yang, Xuejiao Song, Guangwen Yang, Xiaodan Su, Yongbin Mou, Zhaogang Teng, Heng Dong
Journal: Advanced Healthcare Materials (2023)

Traditional dendritic cell (DC)-mediated immunotherapy is usually suppressed by weak immunogenicity in tumors and generally leads to unsatisfactory outcomes. Synergistic exogenous/endogenous immunogenic activation can provide an alternative strategy for evoking a robust immune response by promoting DC activation. Herein, Ti
Letter regarding “Palliative care and end-of-life care in adults with malignant brain tumors”
Authors: Jantine Geertruida Röttgering, Martin Klein, Linda Douw
Journal: Neuro-Oncology (2023)

Journal Article Letter regarding “Palliative care and end-of-life care in adults with malignant brain tumors” Get access Jantine Geertruida Röttgering, Jantine Geertruida Röttgering Cancer Center Amsterdam, Brain Tumor Center, Amsterdam, The NetherlandsAmsterdam UMC Location Vrije Universiteit Amsterdam, Medical Psychology, Boelelaan 1117, Amsterdam, The Netherlands Corresponding Author: Jantine Geertruida Röttgering, MSc, Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Medical Psychology, Boelelaan 1117, 1081HV Amsterdam, The Netherlands (j.rottgering@amsterdamumc.nl) https://orcid.org/0000-0002-9392-3239 Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin Klein, Martin Klein Cancer Center Amsterdam, Brain Tumor Center, Amsterdam, The NetherlandsAmsterdam UMC Location Vrije Universiteit Amsterdam, Medical Psychology, Boelelaan 1117, Amsterdam, The Netherlands https://orcid.org/0000-0001-5553-7911 Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda Douw Linda Douw Cancer Center Amsterdam, Brain Tumor Center, Amsterdam, The NetherlandsAmsterdam UMC location Vrije Universiteit Amsterdam, Anatomy and Neurosciences, Boelelaan 1117, Amsterdam, The Netherlands https://orcid.org/0000-0001-7058-4062 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 3, March 2023, Pages 612–613, https://doi.org/10.1093/neuonc/noad006 Published: 18 February 2023 Article history Corrected and typeset: 18 February 2023 Published: 18 February 2023
Blockade of sphingosine‐1‐phosphate receptor 4 pathway has anti‐inflammatory effects in a murine model of allergic airway inflammation
Authors: Mini Jeong, Sin‐Jeong Kim, Kyomoon Koo, A Ryang Lee, Min Ju Pyo, Hyun Jae Shim, Keun‐Ai Moon, Ji‐Hyang Lee, Chung Hwan Hong, Jae Hyun Kim, Hyunkyung Cho, Eun Hee Koh, Ki‐Up Lee, Sanghee Kim, Sun‐Young Yoon, You‐Sook Cho
Journal: Allergy (2023)

Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Biomimetic Bilayered Scaffolds for Tissue Engineering: From Current Design Strategies to Medical Applications
Authors: Christelle Bertsch, Hélène Maréchal, Varvara Gribova, Benjamin Lévy, Christian Debry, Philippe Lavalle, Léa Fath
Journal: Advanced Healthcare Materials (2023)

Abstract Tissue damage due to cancer, congenital anomalies, and injuries needs new efficient treatments that allow tissue regeneration. In this context, tissue engineering shows a great potential to restore the native architecture and function of damaged tissues, by combining cells with specific scaffolds. Scaffolds made of natural and/or synthetic polymers and sometimes ceramics play a key role in guiding cell growth and formation of the new tissues. Monolayered scaffolds, which consist of uniform material structure, are reported as not being sufficient to mimic complex biological environment of the tissues. Osteochondral, cutaneous, vascular, and many other tissues all have multilayered structures, therefore multilayered scaffolds seem more advantageous to regenerate these tissues. In this review, recent advances in bilayered scaffolds design applied to regeneration of vascular, bone, cartilage, skin, periodontal, urinary bladder, and tracheal tissues are focused on. After a short introduction on tissue anatomy, composition and fabrication techniques of bilayered scaffolds are explained. Then, experimental results obtained in vitro and in vivo are described, and their limitations are given. Finally, difficulties in scaling up production of bilayer scaffolds and reaching the stage of clinical studies are discussed when multiple scaffold components are used.
AIEgens/Mitochondria Nanohybrids as Bioactive Microwave Sensitizers for Non‐Thermal Microwave Cancer Therapy
Authors: Xinghua Yu, Ming Lyu, Xupei Ou, Wenquan Liu, Xing Yang, Xiaoxi Ma, Tianfu Zhang, Longnan Wang, Ying‐Chuan Zhang, Sijie Chen, Ryan T. K. Kwok, Zheng Zheng, Hong‐Liang Cui, Lintao Cai, Pengfei Zhang, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2023)

Abstract Aggregation‐induced emission luminogens (AIEgens) are widely used as photosensitizers for image‐guided photodynamic therapy (PDT). Due to the limited penetration depth of light in biological tissues, the treatments of deep‐seated tumors by visible‐light‐sensitized aggregation‐induced emission (AIE) photosensitizers are severely hampered. Microwave dynamic therapy attracts much attention because microwave irradiation can penetrate very deep tissues and sensitize the photosensitizers to generate reactive oxygen species (ROS). In this work, a mitochondrial‐targeting AIEgen (DCPy) is integrated with living mitochondria to form a bioactive AIE nanohybrid. This nanohybrid can not only generate ROS under microwave irradiation to induce apoptosis of deep‐seated cancer cells but also reprogram the metabolism pathway of cancer cells through retrieving oxidative phosphorylation (OXPHOS) instead of glycolysis to enhance the efficiency of microwave dynamic therapy. This work demonstrates an effective strategy to integrate synthetic AIEgens and natural living organelles, which would inspire more researchers to develop advanced bioactive nanohybrids for cancer synergistic therapy.
Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: a campus CLL study
Authors: Riccardo Bomben, Francesca Maria Rossi, Filippo Vit, Tamara Bittolo, Antonella Zucchetto, Robel Papotti, Erika Tissino, Federico Pozzo, Massimo Degan, Jerry Polesel, Pietro Bulian, Roberto Marasca, Gianluigi Reda, Luca Laurenti, Jacopo Olivieri, Annalisa Chiarenza, Roberta Laureana, Massimiliano Postorino, Maria Ilaria Del Principe, Antonio Cuneo, Massimo Gentile, Fortunato Morabito, Gilberto Fronza, Agostino Tafuri, Francesco Zaja, Robin Foà, Francesco Di Raimondo, Giovanni Del Poeta, Valter Gattei
Journal: Leukemia (2023)
Is it time we changed the way we manage melanoma <i>in situ</i> of the trunk and limbs?
Authors: Hayley Smith, Walayat Hussain
Journal: British Journal of Dermatology (2023)

There is little evidence on the optimal clinical and histological margins required to reduce local recurrence in melanoma in situ (MIS). Our aim was to identify the number of lesions on the trunk and limbs with histological clearance &amp;gt; 1 mm after initial narrow-margin excision. In our cohort 93.6% were considered clear after initial exclusion with no residual MIS seen when further wide local excision was carried out.
Survival of TP53-mutated acute myeloid leukemia patients receiving allogeneic stem cell transplantation after first induction or salvage therapy: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Authors: Talha Badar, Ehab Atallah, Rory Shallis, Antoine N. Saliba, Anand Patel, Jan P. Bewersdorf, Justin Grenet, Maximilian Stahl, Adam Duvall, Madelyn Burkart, Neil Palmisiano, Danielle Bradshaw, Michal Kubiak, Shira Dinner, Aaron D. Goldberg, Yasmin Abaza, Guru Subramanian Guru Murthy, Vamsi Kota, Mark R. Litzow
Journal: Leukemia (2023)
High expression of an intragenic long noncoding RNA misinterpreted as high FTO oncogene expression in NPM1 mutant acute myeloid leukemia
Authors: Saioa Arza-Apalategi, Branco M. H. Heuts, Meike T. M. Dooijes, Daan Gilissen, Adrian J. P. van der Heijden, Joop H. Jansen, Joost H. A. Martens, Bert A. van der Reijden
Journal: Leukemia (2023)
Correction : LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p/c-Myc axis
Authors: Qian Hua, Mingming Jin, Baoming Mi, Fei Xu, Tian Li, Li Zhao, Jianjun Liu, Gang Huang
Journal: Journal of Hematology & Oncology (2023)

The original version of
A Nrf2-OSGIN1&amp;2-HSP70 axis mediates cigarette smoke-induced endothelial detachment: implications for plaque erosion
Authors: Sandro Satta, Robert Beal, Rhys Smith, Xing Luo, Glenn R Ferris, Alex Langford-Smith, Jack Teasdale, Tom Tanjeko Ajime, Jef Serré, Georgina Hazell, Graciela Sala Newby, Jason L Johnson, Svitlana Kurinna, Martin J Humphries, Ghislaine Gayan-Ramirez, Peter Libby, Hans Degens, Bo Yu, Thomas Johnson, Yvonne Alexander, Haibo Jia, Andrew C Newby, Stephen J White
Journal: Cardiovascular Research (2023)

Abstract Aims Endothelial erosion of plaques is responsible for ∼30% of acute coronary syndromes (ACS). Smoking is a risk factor for plaque erosion, which most frequently occurs on the upstream surface of plaques where the endothelium experiences elevated shear stress. We sought to recreate these conditions in vitro to identify potential pathological mechanisms that might be of relevance to plaque erosion. Methods and results Culturing human coronary artery endothelial cells (HCAECs) under elevated flow (shear stress of 7.5 Pa) and chronically exposing them to cigarette smoke extract (CSE) and tumour necrosis factor-alpha (TNFα) recapitulated a defect in HCAEC adhesion, which corresponded with augmented Nrf2-regulated gene expression. Pharmacological activation or adenoviral overexpression of Nrf2 triggered endothelial detachment, identifying Nrf2 as a mediator of endothelial detachment. Growth/Differentiation Factor-15 (GDF15) expression was elevated in this model, with protein expression elevated in the plasma of patients experiencing plaque erosion compared with plaque rupture. The expression of two Nrf2-regulated genes, OSGIN1 and OSGIN2, was increased by CSE and TNFα under elevated flow and was also elevated in the aortas of mice exposed to cigarette smoke in vivo. Knockdown of OSGIN1&amp;2 inhibited Nrf2-induced cell detachment. Overexpression of OSGIN1&amp;2 induced endothelial detachment and resulted in cell cycle arrest, induction of senescence, loss of focal adhesions and actin stress fibres, and disturbed proteostasis mediated in part by HSP70, restoration of which reduced HCAEC detachment. In ACS patients who smoked, blood concentrations of HSP70 were elevated in plaque erosion compared with plaque rupture. Conclusion We identified a novel Nrf2-OSGIN1&amp;2-HSP70 axis that regulates endothelial adhesion, elevated GDF15 and HSP70 as biomarkers for plaque erosion in patients who smoke, and two therapeutic targets that offer the potential for reducing the risk of plaque erosion.
Retraction notice to “In vitro and in vivo evaluation of degradation, toxicity, biodistribution, and clearance of silica nanoparticles as a function of size, porosity, density, and composition” [Journal of Controlled Release 311–312 (2019) Pages 1-15]
Authors: Seyyed Pouya Hadipour Moghaddam, Raziye Mohammadpour, Hamidreza Ghandehari
Journal: Journal of Controlled Release (2023)
Delivery of mitochondria confers cardioprotection through mitochondria replenishment and metabolic compliance
Authors: Alian Zhang, Yangyang Liu, Jianan Pan, Francesca Pontanari, Andrew Chia-Hao Chang, Honghui Wang, Shuang Gao, Changqian Wang, Alex CY. Chang
Journal: Molecular Therapy (2023)

Mitochondrial dysfunction is a hallmark of heart failure. Mitochondrial transplantation has been demonstrated to be able to restore heart function, but its mechanism of action remains unresolved. Using an in-house optimized mitochondrial isolation method, we tested efficacy of mitochondria transplantation in two different heart failure models. First, using a doxorubicin-induced heart failure model, we demonstrate that mitochondrial transplantation before doxorubicin challenge protects cardiac function in vivo and prevents myocardial apoptosis, but contraction improvement relies on the metabolic compatibility between transplanted mitochondria and treated cardiomyocytes. Second, using a mutation-driven dilated cardiomyopathic human induced pluripotent stem cell-derived cardiomyocyte model, we demonstrate that mitochondrial transplantation preferentially boosts contraction in the ventricular myocytes. Last, using single-cell RNA-seq, we show that mitochondria transplantation boosts contractility in dystrophic cardiomyocytes with few transcriptomic alterations. Together, we provide evidence that mitochondria transplantation confers myocardial protection and may serve as a potential therapeutic option for heart failure. Mitochondrial dysfunction is a hallmark of heart failure. Mitochondrial transplantation has been demonstrated to be able to restore heart function, but its mechanism of action remains unresolved. Using an in-house optimized mitochondrial isolation method, we tested efficacy of mitochondria transplantation in two different heart failure models. First, using a doxorubicin-induced heart failure model, we demonstrate that mitochondrial transplantation before doxorubicin challenge protects cardiac function in vivo and prevents myocardial apoptosis, but contraction improvement relies on the metabolic compatibility between transplanted mitochondria and treated cardiomyocytes. Second, using a mutation-driven dilated cardiomyopathic human induced pluripotent stem cell-derived cardiomyocyte model, we demonstrate that mitochondrial transplantation preferentially boosts contraction in the ventricular myocytes. Last, using single-cell RNA-seq, we show that mitochondria transplantation boosts contractility in dystrophic cardiomyocytes with few transcriptomic alterations. Together, we provide evidence that mitochondria transplantation confers myocardial protection and may serve as a potential therapeutic option for heart failure.
A high-fidelity RNA-targeting Cas13 restores paternal Ube3a expression and improves motor functions in Angelman syndrome mice
Authors: Jinhui Li, Zhixin Shen, Yajing Liu, Zixiang Yan, Yuanhua Liu, Xiang Lin, Junjie Tang, Ruimin Lv, Guannan Geng, Zhi-Qi Xiong, Changyang Zhou, Hui Yang
Journal: Molecular Therapy (2023)

Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function mutations in maternally expressed UBE3A. No gene-specific treatment is available for patients so far. Although intact and transcriptionally active, paternally inherited UBE3A is silenced by elongation of antisense long noncoding RNA UBE3A-ATS in neurons. Here, we demonstrated that RNA targeting of paternal Ube3a-ATS with a high-fidelity CRISPR-Cas13 (hfCas13x.1) system could restore Ube3a expression to similar levels as that of maternal Ube3a in the cultured mouse neurons. Furthermore, injection into lateral ventricles with neuron-specific hSyn1 promoter-driven hfCas13x.1 packaged in adeno-associated virus (AAV-PHP.eb) could restore paternal Ube3a expression in cortex and hippocampus of neonatal AS mice for up to 4 months after treatment. Behavioral tests showed that expression of paternal Ube3a significantly alleviated AS-related symptoms, including obesity and motor function. Our results suggested that hfCas13x.1-mediated suppression of the Ube3a-ATS lncRNA potentially serves as a promising targeted intervention for AS.
Predicting gene mutation status via artificial intelligence technologies based on multimodal integration (MMI) to advance precision oncology
Authors: Jun Shao, Jiechao Ma, Qin Zhang, Weimin Li, Chengdi Wang
Journal: Seminars in Cancer Biology (2023)

Personalized treatment strategies for cancer frequently rely on the detection of genetic alterations which are determined by molecular biology assays. Historically, these processes typically required single-gene sequencing, next-generation sequencing, or visual inspection of histopathology slides by experienced pathologists in a clinical context. In the past decade, advances in artificial intelligence (AI) technologies have demonstrated remarkable potential in assisting physicians with accurate diagnosis of oncology image-recognition tasks. Meanwhile, AI techniques make it possible to integrate multimodal data such as radiology, histology, and genomics, providing critical guidance for the stratification of patients in the context of precision therapy. Given that the mutation detection is unaffordable and time-consuming for a considerable number of patients, predicting gene mutations based on routine clinical radiological scans or whole-slide images of tissue with AI-based methods has become a hot issue in actual clinical practice. In this review, we synthesized the general framework of multimodal integration (MMI) for molecular intelligent diagnostics beyond standard techniques. Then we summarized the emerging applications of AI in the prediction of mutational and molecular profiles of common cancers (lung, brain, breast, and other tumor types) pertaining to radiology and histology imaging. Furthermore, we concluded that there truly exist multiple challenges of AI techniques in the way of its real-world application in the medical field, including data curation, feature fusion, model interpretability, and practice regulations. Despite these challenges, we still prospect the clinical implementation of AI as a highly potential decision-support tool to aid oncologists in future cancer treatment management.
Phase I study of liver depot gene therapy in late-onset Pompe disease
Authors: Edward C. Smith, Sam Hopkins, Laura E. Case, Ming Xu, Crista Walters, Stephanie Dearmey, Sang-oh Han, Tracy G. Spears, Jessica A. Chichester, Edward H. Bossen, Christoph P. Hornik, Jennifer L. Cohen, Deeksha Bali, Priya S. Kishnani, Dwight D. Koeberl
Journal: Molecular Therapy (2023)

Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement therapy (ERT) by creating a liver depot for acid α-glucosidase (GAA) production. We report initial safety and bioactivity of the first dose (1.6 × 10
Reprint of: Clearance of multiple cutaneous warts by targeting a single lesion: A randomized comparative evaluation of mild local hyperthermia versus cryotherapy
Authors: Rui-Qun Qi, Junfeng Zhou, Bihuan Xiao, Honghui Xu, Shuai Qiao, Peiyao Zhu, Lixin Xia, Yang Yang, Li Zhang, Hongwei Yan, Congcong He, Yuzhe Sun, Xueli Niu, Yuqing Zhang, Lingyu Fu, Xiuli Wang, Hong-Duo Chen, Shanshan Li, Xing-Hua Gao
Journal: Journal of the American Academy of Dermatology (2023)
A multinational cohort study uncovered sex differences in excess mortality after kidney transplant
Authors: Amanda J. Vinson, Xun Zhang, Mourad Dahhou, Caner Süsal, Bernd Döhler, Anette Melk, Ruth Sapir-Pichhadze, Heloise Cardinal, Germaine Wong, Anna Francis, Helen Pilmore, Bethany J. Foster
Journal: Kidney International (2023)
Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study
Authors: Heng‐Chung Kung, Jun Yu
Journal: MedComm (2023)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a high rate of recurrence and a dismal 5‐year survival rate. Contributing to the poor prognosis of PDAC is the lack of early detection, a complex network of signaling pathways and molecular mechanisms, a dense and desmoplastic stroma, and an immunosuppressive tumor microenvironment. A recent shift toward a neoadjuvant approach to treating PDAC has been sparked by the numerous benefits neoadjuvant therapy (NAT) has to offer compared with upfront surgery. However, certain aspects of NAT against PDAC, including the optimal regimen, the use of radiotherapy, and the selection of patients that would benefit from NAT, have yet to be fully elucidated. This review describes the major signaling pathways and molecular mechanisms involved in PDAC initiation and progression in addition to the immunosuppressive tumor microenvironment of PDAC. We then review current guidelines, ongoing research, and future research directions on the use of NAT based on randomized clinical trials and other studies. Finally, the current use of and research regarding targeted therapy for PDAC are examined. This review bridges the molecular understanding of PDAC with its clinical significance, development of novel therapies, and shifting directions in treatment paradigm.
Advances in Gelatin Bioinks to Optimize Bioprinted Cell Functions
Authors: Saad Asim, Tanveer A. Tabish, Usman Liaqat, Ibrahim T. Ozbolat, Muhammad Rizwan
Journal: Advanced Healthcare Materials (2023)

Gelatin is a widely utilized bioprinting biomaterial due to its cell-adhesive and enzymatically cleavable properties, which improve cell adhesion and growth. Gelatin is often covalently cross-linked to stabilize bioprinted structures, yet the covalently cross-linked matrix is unable to recapitulate the dynamic microenvironment of the natural extracellular matrix (ECM), thereby limiting the functions of bioprinted cells. To some extent, a double network bioink can provide a more ECM-mimetic, bioprinted niche for cell growth. More recently, gelatin matrices are being designed using reversible cross-linking methods that can emulate the dynamic mechanical properties of the ECM. This review analyzes the progress in developing gelatin bioink formulations for 3D cell culture, and critically analyzes the bioprinting and cross-linking techniques, with a focus on strategies to optimize the functions of bioprinted cells. This review discusses new cross-linking chemistries that recapitulate the viscoelastic, stress-relaxing microenvironment of the ECM, and enable advanced cell functions, yet are less explored in engineering the gelatin bioink. Finally, this work presents the perspective on the areas of future research and argues that the next generation of gelatin bioinks should be designed by considering cell-matrix interactions, and bioprinted constructs should be validated against currently established 3D cell culture standards to achieve improved therapeutic outcomes.